Activity of gelatins to induce secretion of a variety of cytokines from murine peritoneal exudate macrophages.

Previously, we observed that liquid form bovine bone (BB) gelatin stimulates murine spleen cells to proliferate in vitro. In this study, activity of BB gelatin to stimulate murine-adherent peritoneal exudate cells (PEC) to secrete cytokines has been examined. Quantitatively, BB gelatin stimulated adherent PEC of C3H/HeN mice to secrete interleukin (IL)-12 (+p40), TNF-alpha, and IL-6 but not IL-1beta, IL-2, IL-10, and IFN-gamma. Qualitatively, BB gelatin-induced secretion of KC, MIP-2, MCP-1, RANTES, and MIP-1a as well as IL-6 but not 6Ckine, CTACK, Eotaxin, G-CSF, GM-CSF, IL-2,-3,-4,-5,-9,-10,-12,-13,-17, Leptin, IFN-gamma, SCF, sTNFri, TARC, TNF-alpha, TIMP-1, Tpo, and VEGF. BB gelatin acted on adherent PEC of C3H/HeN mice but not C3H/HeJ mice, which lack Toll-like receptor 4. Polymyxin B, a LPS antagonist, did not inhibit the activity of BB gelatin. Lipopolysaccharide (LPS) but not BB gelatin induced secretion of an appreciable amount of mIL-1beta. These results suggest that the activity of BB gelatin is not attributed to contamination of LPS but BB gelatin itself. It was also suggested that BB gelatin stimulated adherent PEC to newly produce and secrete cytokines.

Comparison between bovine bone and porcine skin gelatins in their effects on murine cell proliferation.

We investigated relationship between porcine skin (PS) and bovine bone (BB) gelatins in their actions on proliferation of murine benign and malignant cells in this study. We previously observed that BB gelatin enhanced spleen cell proliferation. The present study showed that such an activity of BB gelatin was not exerted in a serum-free medium. On the other hand, PS gelatin suppressed proliferation of normal spleen cells and of those stimulated by concanavalin A (Con A). It is not known whether or not such an activity of PS gelatin on Con A-stimulated spleen cells is exerted in the serum-free medium since Con A was unable to augment proliferation of spleen cells in that medium. BB gelatin as well as PS gelatin suppressed proliferation of RL male symbol 1 cells, a T cell lymphoma cell line of Balb/c mice, and such an activity of BB gelatin was not exerted in the serum-free medium whereas PS gelatin exerted its activity in the same medium. Mitomycin C (MMC)-treated spleen cells as well as MMC-treated RL male symbol 1 cells partly released RL male symbol 1 cells from the inhibition of proliferation by PS gelatin. MMC-treated RL male symbol 1 cells as well as MMC-treated spleen cells suppressed the proliferation of spleen cells augmented by BB gelatin. Inhibition of RL male symbol 1 cell proliferation by PS gelatin was not affected by BB gelatin, but enhancement of spleen cell proliferation by BB gelatin was attenuated by PS gelatin regardless of the sequence of treating the spleen cells with PS gelatin. Enhancement of spleen cell proliferation by BB gelatin was time-dependent but suppression of RL male symbol 1 cell proliferation by PS gelatin was not. In conclusion, BB gelatin enhanced proliferation of spleen cells and suppressed proliferation of RL male symbol 1 cells. In both cases, fetal calf serum (FCS) was required. PS gelatin suppressed proliferation of spleen cells and of RL male symbol 1 cells without FCS.

Expression of somatostatin receptor and effects of somatostatin analog on pancreatic endocrine tumors.

PURPOSE: Somatostatin analogs have been administered to patients with pancreatic endocrine tumors in an attempt to inhibit hormone hypersecretion and prevent tumor growth. It is speculated that their efficacy is correlated with the expression of specific subtypes of somatostatin receptors. The aim of this study was to immunohistochemically evaluate the expression of somatostatin receptor subtypes in human pancreatic endocrine tumors, and to determine whether the expression of these subtypes is correlated with the effectiveness of the somatostatin analogs. METHODS: Somatostatin receptor subtypes 1, 2, and 3 (sst 1, 2, and 3) were immunohistochemically investigated in seven pancreatic endocrine tumors: four insulinomas, one VIPoma, and two nonfunctioning tumors associated with multiple endocrine neoplasia type I, using paraffin sections. Three of the four patients with insulinoma were given an octreotide injection. RESULTS: Cells were homogeneously stained in the tumor region. More than 85% of the specimens expressed sst 1, 2, and 3. There was no difference among the immunohistochemical stainings of somatostatin receptor subtypes according to most tumor characteristics; however, the expression of sst 2 was extremely positive, and the expression of sst 3 was moderately positive in the specimen from a patient in whom the octreotide injection had proven very effective. CONCLUSION: These findings indicate that the efficacy of octreotide may be correlated with the density of sst 2 and 3 in an immunohistological study using paraffin sections.